A comprehensive interdisciplinary group composed of synthetic chemists, biochemists, virologists, biophysical chemists, pharmacologists and primate biologists, based upon preliminary data presented herein, propose novel structures to be used for control of human immunodeficiency viruses (HIV) infections. Preliminary data on potential anti-HIV agents which include porphyrins, metalloporphyrins, heteropolyarenes, aryl diimides and aryl diamidines are described in Projects 1-3 of this proposal. These anti-retroviral agents and the new compounds proposed for synthesis will be fully evaluated, through the Biological Core and Project 4, involving a rational progression starting with in vitro screens and including biophysical, biochemical, pharmacological and toxicological investigations concluding with in vivo assessments employing mouse and nonhuman primate models. Our group will be able to provide a comprehensive approach to developing new, effective anti-HIV agents by synthesis of new compounds, by determination of antiviral activity in cell culture and in animal models, and by biochemical and pharmacological evaluation of the effects of these compounds on both the host and the virus.